scholarly journals Determination of Non-α1-Antichymotrypsin-complexed Prostate-specific Antigen as an Indirect Measurement of Free Prostate-specific Antigen: Analytical Performance and Diagnostic Accuracy

2003 ◽  
Vol 49 (6) ◽  
pp. 887-894 ◽  
Author(s):  
Sebastian Wesseling ◽  
Carsten Stephan ◽  
Axel Semjonow ◽  
Michael Lein ◽  
Brigitte Brux ◽  
...  
Keyword(s):  
Prostate Specific Antigen ◽  
Sensitivity And Specificity ◽  
Specific Antigen ◽  
Roc Curves ◽  
Indirect Measurement ◽  
Free Psa ◽  
Specificity And Sensitivity ◽  
Diagnostic Sensitivity And Specificity ◽  
Total Psa

Abstract Background: A new assay measures prostate-specific antigen (PSA) not complexed to α1-antichymotrypsin (nACT-PSA) after removing PSA complexed to ACT by use of anti-ACT antibodies. We evaluated nACT-PSA and its ratio to total PSA (tPSA) as alternatives to free PSA (fPSA) and its ratio to tPSA in differentiating prostate cancer (PCa) and benign prostatic hyperplasia (BPH) in patients with tPSA of 2–20 μg/L. Methods: PSA in serum of 183 untreated patients with PCa and 132 patients with BPH was measured retrospectively on the chemiluminescence immunoassay analyzer LIAISON® (Byk-Sangtec Diagnostica) with the LIAISON tPSA and LIAISON fPSA assays. The nACT-PSA fraction was determined with a prototype assay measuring the residual PSA after precipitation of ACT-PSA with an ACT-precipitating reagent. Results:nACT-PSA was higher than fPSA in samples with fPSA concentrations <1 μg/L but lower in samples with >1 μg/L fPSA. The median ratios of fPSA/tPSA and of nACT-PSA/tPSA were significantly different between patients with BPH and PCa (19.4% vs 12.2% and 17.4% vs 13.0%, respectively). Within the tPSA ranges tested (2–20, 2–10, and 4–10 μg/L), areas under the ROC curves for the fPSA/tPSA ratios were significantly larger than those for nACT-PSA/tPSA. In the tPSA ranges <10 μg/L, the areas under the ROC curves for fPSA/tPSA were significantly larger than those for tPSA, whereas the areas for nACT-PSA/tPSA were not. At decision limits for 95% sensitivity and specificity, both ratios significantly increased specificity and sensitivity, respectively, compared with tPSA, but the fPSA/tPSA ratio showed higher values. Conclusions: nACT-PSA and its ratio to tPSA provide lower diagnostic sensitivity and specificity than fPSA/tPSA. The fPSA/tPSA ratio represents the state-of-the-art method for differentiating between PCa and BPH.

scholarly journals Analytical performance of the Tandem®-R free PSA immunoassay measuring free prostate-specific antigen

1997 ◽  
Vol 43 (7) ◽  
pp. 1203-1208 ◽  
Author(s):  
David L Woodrum ◽  
Chester M French ◽  
Timothy M Hill ◽  
Steven J Roman ◽  
Harold L Slatore ◽  
...  
Keyword(s):  
Prostate Specific Antigen ◽  
Accurate Determination ◽  
Specific Antigen ◽  
Cross Reactivity ◽  
Analytical Performance ◽  
Minimum Detectable Concentration ◽  
Free Psa ◽  
Detectable Concentration ◽  
Total Psa

Abstract The analytical performance of the Tandem®-R free PSA assay available from Hybritech Inc. was evaluated. Comparison of recoveries of purified free (unbound) prostate-specific antigen (PSA) diluted in female serum in the Tandem-R free PSA assay and the Tandem-R (total) PSA assay demonstrated a link in calibration between the assays and an accurate determination of percent free PSA. The cross-reactivity of the assay to purified PSA–α1-antichymotrypsin was determined to be <1%. The minimum-detectable concentration was <0.05 μg/L. The within-run and between-day CVs were ≤5% for samples with >0.3 μg/L free PSA. Dilution and recovery showed no significant deviations from linearity across the assay range. The assay was insensitive to interference from blood components. The Tandem-R free PSA kit was shown to be an accurate, precise, and reliable assay for the measurement of free PSA.

scholarly journals Measurement of the Complex between Prostate-specific Antigen and α1-Protease Inhibitor in Serum

1999 ◽  
Vol 45 (6) ◽  
pp. 814-821 ◽  
Author(s):  
Wan-Ming Zhang ◽  
Patrik Finne ◽  
Jari Leinonen ◽  
Satu Vesalainen ◽  
Stig Nordling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protease Inhibitor ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Serum Samples ◽  
Free Psa ◽  
Total Psa ◽  
Healthy Females

Abstract Background: Prostate-specific antigen (PSA) occurs in serum both free and in complex with protease inhibitors. The complex with α1-antichymotrypsin (ACT) is the major form in serum, and the proportion of PSA-ACT is higher in prostate cancer (PCa) than in benign prostatic hyperplasia (BPH). PSA also forms a complex with α1-protease inhibitor (API) in vitro, and the PSA-ACT complex has been detected in serum from patients with prostate cancer. The aim of the present study was to develop a quantitative method for the determination of PSA-API and to determine the serum concentrations in patients with PCa and BPH. Methods: The assay for PSA-API utilizes a monoclonal antibody to PSA as capture and a polyclonal antibody to API labeled with a Eu-chelate as a tracer. For calibrators, PSA-API formed in vitro was used. Serum samples were obtained before treatment from 82 patients with PCa, from 66 patients with BPH, and from 22 healthy females. Results: The concentrations of PSA-API are proportional to the concentrations of total PSA. PSA-API comprises 1.0–7.9% (median, 2.4%) of total immunoreactive PSA in PCa and 1.3–12.2% (median, 3.6%) in BPH patients with serum PSA concentrations >4 μg/L. In patients with 4–20 μg/L total PSA, the proportion of PSA-API serum is significantly higher in BPH (median, 4.1%) than in PCa (median, 3.2%; P = 0.02). Conclusions: The proportion of PSA-API in serum is lower in patients with PCa than in those with BPH. These results suggest that PSA-API is a potential adjunct to total and free PSA in the diagnosis of prostate cancer.

scholarly journals Between-Method Differences in Prostate-Specific Antigen Assays Affect Prostate Cancer Risk Prediction by Nomograms

2011 ◽  
Vol 57 (7) ◽  
pp. 995-1004 ◽  
Author(s):  
Carsten Stephan ◽  
Kerstin Siemßen ◽  
Henning Cammann ◽  
Frank Friedersdorff ◽  
Serdar Deger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Risk Prediction ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Roc Curves ◽  
Median Percentage ◽  
Free Psa ◽  
Different Types ◽  
Total Psa

BACKGROUND To date, no published nomogram for prostate cancer (PCa) risk prediction has considered the between-method differences associated with estimating concentrations of prostate-specific antigen (PSA). METHODS Total PSA (tPSA) and free PSA were measured in 780 biopsy-referred men with 5 different assays. These data, together with other clinical parameters, were applied to 5 published nomograms that are used for PCa detection. Discrimination and calibration criteria were used to characterize the accuracy of the nomogram models under these conditions. RESULTS PCa was found in 455 men (58.3%), and 325 men had no evidence of malignancy. Median tPSA concentrations ranged from 5.5 μg/L to 7.04 μg/L, whereas the median percentage of free PSA ranged from 10.6% to 16.4%. Both the calibration and discrimination of the nomograms varied significantly across different types of PSA assays. Median PCa probabilities, which indicate PCa risk, ranged from 0.59 to 0.76 when different PSA assays were used within the same nomogram. On the other hand, various nomograms produced different PCa probabilities when the same PSA assay was used. Although the ROC curves had comparable areas under the ROC curve, considerable differences were observed among the 5 assays when the sensitivities and specificities at various PCa probability cutoffs were analyzed. CONCLUSIONS The accuracy of the PCa probabilities predicted according to different nomograms is limited by the lack of agreement between the different PSA assays. This difference between methods may lead to unacceptable variation in PCa risk prediction. A more cautious application of nomograms is recommended.

scholarly journals CAN PROSTATE-SPECIFIC ANTIGEN DENSITY AND FREE / TOTAL PROSTATE-SPECIFIC ANTIGEN RATIO PREDICT CLINICALLY SIGNIFICANT PROSTATE CANCER (GLEASON ≥ 7) IN PATİENTS DIAGNOSED PROSTATE CANCER ON BIOPSY WITH A PROSTATE-SPECIFIC ANTIGEN LEVEL OF 2.5 -10 NG/ML?

2021 ◽  
Author(s):  
Fatih Bicaklioglu ◽  
Hasan Aydin ◽  
Ahmet Özgür Güçtaş ◽  
Hamit Zafer Aksoy
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Sensitivity And Specificity ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Free Psa ◽  
Total Prostate Specific Antigen ◽  
Prostate Specific Antigen Density ◽  
Clinically Significant ◽  
Total Psa

Introduction Many men with non-clinically significant PCa (N-CSPCa) will not progress to become symptomatic within their lifetime. If we can predict clinically significant PCa (CSPCa), we can prevent patients from unnecessary biopsies, overdiagnoses, and overtreatment. The purpose of this study was to determine whether PSAD and f/t PSA can predict CSPCa (Gleason ≥ 7) in patients diagnosed with prostate cancer on biopsy with a PSA level of 2.5-10 ng/ml or not. Materials and Methods 78 patients who underwent TRUSG-guided prostate biopsy with PSA 2.5-10.0 in our clinic between March 2017 - August 2020 and whose pathology result was reported as prostate adenocarcinoma, were retrospectively evaluated. In addition to the demographic content of the patients, PSA, free PSA, prostate size (with TRUSG), rectal examination findings and prostate biopsy pathology results were recorded. Clinically significant prostate cancer was defined as a Gleason score 7. Results The mean age of the patients was 66.9 ± 8.4, PSA value was 6.9 ± 1.8, free / total PSA ratio was 18 ± 8.1%, and PSA density was 0.150 ± 0.078. The P values of PSA, free PSA, PSAD, f/t PSA, and prostate volume between CSPCa and N- CSPCa groups were 0.010, 0.780, 0.001, 0.084, and 0.030, respectively. The area under the ROC curve (AUC) of the PSAD for predicting CSPCa was 0.719 with a 95% Cl (0.604–0.835), and the standard errors were 0.062 and 0.059, respectively. When PSAD cutoff was 0.130 for predicting CSPCa, sensitivity and specificity were 75% and 63%, respectively. Conclusion PSAD can be used for predicting CSPCa, but f/t PSA can not. PSAD is not a strong stand-alone tool with its sensitivity and specificity, but we suggest that PSAD can be a part of future nomograms for predicting CSPCa and future protocols for active surveillance. Key words:prostate-specific antigen; clinically significant prostate cancer

Effect of Marathon Running on Total and Free Serum Prostate-Specific Antigen Concentrations

2003 ◽  
Vol 127 (3) ◽  
pp. 345-348 ◽  
Author(s):  
Alexander Kratz ◽  
Kent B. Lewandrowski ◽  
Arthur J. Siegel ◽  
Patrick M. Sluss ◽  
Kelly Y. Chun ◽  
...  
Keyword(s):  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Physical Exertion ◽  
The United States ◽  
Marathon Running ◽  
Reliable Determination ◽  
Free Psa ◽  
Sporting Event ◽  
Exercise Induced ◽  
Total Psa

Abstract Context.—Prostate-specific antigen (PSA) is an important tumor marker for the most frequently diagnosed cancer in the United States. A major limitation of this marker is falsely elevated results in patients who are found not to have prostate cancer. The effects of vigorous physical exertion on PSA concentrations are controversial. Objective.—To determine the effects of marathon running on PSA levels. Design.—Measurement of total and free PSA levels in the sera of participants in a marathon before and within 4 and 24 hours after the race. Results.—None of the participants had elevated total PSA levels before the race. Although we found no statistically significant changes in average total or free PSA concentrations at either time point, after the marathon, 2 (11%) of 18 runners had total PSA concentrations outside the standard reference range. Changes in total PSA levels did not correlate with age or prerace PSA concentrations. Free PSA levels were not statistically significantly changed after the race and did not allow a reliable determination of exercise-induced PSA elevations. Conclusions.—Although it may not be necessary for men to abstain from exercise involving running before blood draws for PSA analysis, elevated PSA concentrations may be observed in some individuals after participation in a major sporting event. In these cases, repeat measurements should be considered at a time significantly removed from such exercise.

scholarly journals The Combination of Human Glandular Kallikrein and Free Prostate-specific Antigen (PSA) Enhances Discrimination Between Prostate Cancer and Benign Prostatic Hyperplasia in Patients with Moderately Increased Total PSA

1999 ◽  
Vol 45 (11) ◽  
pp. 1960-1966 ◽  
Author(s):  
Angeliki Magklara ◽  
Andreas Scorilas ◽  
William J Catalona ◽  
Eleftherios P Diamandis
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Prostate Specific Antigen ◽  
Prostatic Carcinoma ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Prostatic Hyperplasia ◽  
Free Psa ◽  
Glandular Kallikrein ◽  
Total Psa

Abstract Background: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4–10 μg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic “gray zone”. Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. Methods: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5–10 μg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. Results: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5–10 μg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 μg/L who had cancer. Conclusions: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 μg/L who have high probability of cancer and who should be considered for biopsy.

Dual-label one-step immunoassay for simultaneous measurement of free and total prostate-specific antigen concentrations and ratios in serum

1995 ◽  
Vol 41 (8) ◽  
pp. 1115-1120 ◽  
Author(s):  
K Mitrunen ◽  
K Pettersson ◽  
T Piironen ◽  
T Björk ◽  
H Lilja ◽  
...  
Keyword(s):  
Prostate Specific Antigen ◽  
Simultaneous Measurement ◽  
Solid Phase ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Sample Volume ◽  
Free Psa ◽  
One Step ◽  
Total Psa ◽  
Dual Label

Abstract We developed a simple one-step dual-label immunoassay for simultaneous measurement of the free, noncomplexed form of prostate-specific antigen (PSA) and total PSA. The assay is based on time-resolved fluorescence and includes a stable fluorescent chelate of Eu to label a monoclonal antibody (mAb) that detects only free PSA, whereas a second mAb labeled with a fluorescent chelate of Tb provides equimolar detection of both free PSA and PSA complexed to alpha 1-antichymotrypsin. A third mAb on a solid phase captures the free and complexed forms of PSA in an equimolar fashion. The simultaneous measurement of the free-to-total PSA ratio (F/T) with the one-step dual assay is not sensitive to variations in the sample volume. The discrimination between benign prostatic hyperplasia and prostate cancer patients, i.e., the area under the receiver-operating characteristic curve, increased from 0.64 (total PSA assay) to 0.78 and 0.81 when the F/T ratio was measured with single and dual assays, respectively.

scholarly journals Reference Reagents for Prostate-specific Antigen (PSA): Establishment of the First International Standards for Free PSA and PSA (90:10)

2000 ◽  
Vol 46 (9) ◽  
pp. 1310-1317 ◽  
Author(s):  
Brian Rafferty ◽  
Peter Rigsby ◽  
Matthew Rose ◽  
Thomas Stamey ◽  
Rose Gaines Das
Keyword(s):  
Confidence Interval ◽  
Prostate Specific Antigen ◽  
Recombinant Dna ◽  
Collaborative Study ◽  
Specific Antigen ◽  
International Standards ◽  
Serum Samples ◽  
International Standard ◽  
Free Psa ◽  
Total Psa

Abstract Background: Prostate-specific antigen (PSA) measurements in serum by immunoassay are widely used in the screening, diagnosis, and monitoring of patients with prostate cancer although the lack of common reference reagents has led in the past to wide differences in estimates. We report here the results of a WHO international collaborative study in which two preparations of PSA representative of the main immunoreactive components in serum, free PSA and PSA 90:10, and a preparation of recombinant DNA-derived PSA were assessed as potential standards for the calibration of diagnostic immunoassays for PSA. Methods: Coded vials of the candidate materials and serum preparations containing PSA in the clinically important range were provided to the 10 laboratories in the study, and participants were asked to perform PSA assays currently in use in their laboratories. Data from 89 immunoassays by 26 different method-laboratory combinations were contributed to the study and analyzed centrally at the National Institute for Biological Standards and Control. Results: Potency estimates of the preparations relative to the in-house calibrators were in good agreement with the target value of 1 μg of total PSA/vial, the preparation of free PSA giving 1.10 μg/vial (95% confidence interval, 0.99–1.21 μg/vial) and PSA 90:10, 1.11 μg/vial (95% confidence interval, 1.04–1.18 μg/vial). No immunoreactivity was detected in ampoules containing the recombinant material. Use of a common standard of PSA 90:10 significantly reduced the between-laboratory geometric coefficients of variation for serum samples included in the study and gave a much narrower range of potency estimates. Conclusions: The preparation of free PSA was established by WHO as the First International Standard for PSA (free) with an assigned content of 1 μg of total PSA per vial. In addition, the preparation of bound PSA was established as the First International Standard for PSA (90:10) with an assigned content of 1 μg of total PSA per vial.

scholarly journals Proenzyme Forms of Prostate-Specific Antigen in Serum Improve the Detection of Prostate Cancer

2004 ◽  
Vol 50 (6) ◽  
pp. 1017-1025 ◽  
Author(s):  
Stephen D Mikolajczyk ◽  
William J Catalona ◽  
Cindy L Evans ◽  
Harry J Linton ◽  
Lisa S Millar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Cancer Detection ◽  
Specific Antigen ◽  
Serum Markers ◽  
Prostate Cancer Detection ◽  
Good Marker ◽  
Free Psa ◽  
Specificity And Sensitivity ◽  
Benign Prostate

Abstract Introduction: Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively]. Methods: Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA. Sera from patients with prostate cancer or benign prostate disease containing 4–10 μg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity. Results: The proPSA forms had quantification limits of 0.015–0.025 μg/L in serum, with cross-reactivities <1% with PSA. The sum of the proPSA forms divided by free PSA (percentage proPSA) had a higher AUC than did percentage of (-2)proPSA, free PSA, and complexed PSA with AUC (95% confidence intervals) of 0.69 (0.64–0.74), 0.64 (0.58–0.68), 0.63 (0.58–0.68), and 0.57 (0.51–0.62), respectively. The proPSA comprised a median of 33% of the free PSA in cancer and 25% in noncancer sera (P <0.0001). One-third (33%) of cancer samples had >40% proPSA, whereas only 8% of noncancer samples did (P <0.0001). In men with cancer and >25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66–0.86), with 90% sensitivity and 36% specificity at 0.04 μg/L. Conclusions: The percentage of proPSA gave better cancer detection in the 4–10 μg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.

scholarly journals Effect of the Ratio of Free to Total Prostate-specific Antigen on Interassay Variability in Proficiency Test Samples

1999 ◽  
Vol 45 (8) ◽  
pp. 1181-1189 ◽  
Author(s):  
M Pat Fox ◽  
Andrew A Reilly ◽  
Erasmus Schneider
Keyword(s):  
Prostate Specific Antigen ◽  
Proficiency Test ◽  
Seminal Fluid ◽  
Specific Antigen ◽  
Free Form ◽  
Sample Mean ◽  
Substantial Impact ◽  
Free Psa ◽  
Total Prostate Specific Antigen ◽  
Total Psa

Abstract Background: Up to sevenfold differences were observed between total prostate-specific antigen (PSA) methods for New York State Proficiency Test samples prepared with seminal fluid PSA in human female serum. Because the PSA was mainly in its free form under these conditions, we wanted to determine whether a defined mixture of free and complexed PSA would reduce the interassay differences. Methods: We prepared a series of five solutions of 60 g/L bovine serum albumin with 10 μg/L total PSA consisting of varied proportions of free, noncomplexible PSA, and α1-antichymotrypsin (ACT)-complexed PSA from 0% to 100%. Two hundred seventy laboratories measured the total PSA in these samples, and 16 laboratories also analyzed the samples for free PSA. The results were used to calculate free/total PSA ratios. Results: Interassay CVs for total PSA measurements were ∼7% at 10–15% free PSA but became gradually larger as the free/total PSA ratio increased. Measured free-PSA concentrations were similar within each sample (mean CV, 12%), and the results were relatively independent of the proportion of free PSA in the samples. Twofold discrepancies between actual and expected ratios were observed with some methods at 100% free PSA and to a lesser degree at 30% free PSA. At 100% free PSA, the relatively higher total-PSA values measured by nonequimolar methods yielded low free/total PSA ratios of 50–60%. In contrast, the lower total PSA values obtained by equimolar methods yielded ratios close to the expected 100%. Conclusions: Preparing proficiency test samples with a 10:90 mixture of free, noncomplexible PSA:PSA-ACT is a viable alternative to the use of seminal fluid PSA. Furthermore, the method used to measure total PSA may have a substantial impact on the calculated proportion of free PSA and hence may have clinical relevance.

Sign in / Sign up

Export Citation Format

Share Document